[New directions in psychiatric genetics: Genome-wide association studies, polygenic risk score and cross-disorder analysis].

Abstract

The field of psychiatric genetics investigates the genetic background of psychiatric disorders. In a broader sense, this discipline aims to understand the molecular pathways underlying psychopathology, therefore, it is also referred to as molecular psychiatry. The most important question of this field was originally the following: What type of inheritance is responsible for the overrepresentation of psychiatric disorders in certain families, and which variants of the human genome account for the heritability of these disorders? Moreover, can we get closer to understanding the biological mechanisms of psychiatric disorders by studying and identifying such genetic variants? Technological development during the past decades has enabled us to collect, analyze and compare genetic data from large sample sets of patients and healthy control individuals. Genome-wide association studies (GWAS) have identified common variants that convey increased risk of small effect for the development of different psychiatric disorders. Furthermore, we are now able to compose polygenic risk scores (PRS) from these disease-causing variants and quantify the overall genetic risk of individuals. The implementation of this method supports the polygenic nature of psychiatric disorders. Finally, cross-disorder analyses have the potential to compare the genetic background of different psychiatric disorders and to determine overlapping and distinct marker sets between disorders. These new research methods are described in our review paper through the examples of schizophrenia and attention deficit-hyperactivity disorder (ADHD). Psychiatric genetics has not yet entered the everyday clinical practice in psychiatry, however, it informs us about the biological underpinnings and genetic architecture of psychiatric disorders.